Measurement of (13) C turnover into glutamate and glutamine pools in brain tumor patients

测量脑肿瘤患者体内(13)C向谷氨酸和谷氨酰胺池的转化

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Abstract

Malignant brain tumors are known to utilize acetate as an alternate carbon source in the citric acid cycle for their bioenergetics. (13) C NMR-based isotopomer analysis has been used to measure turnover of (13) C-acetate carbons into glutamate and glutamine pools in tumors. Plasma from the patients infused with [1,2-(13) C]acetate further revealed the presence of (13) C isotopomers of glutamine, glucose, and lactate in the circulation that were generated due to metabolism of [1,2-(13) C]acetate by peripheral organs. In the tumor cells, [4-(13) C] and [3,4-(13) C]glutamate and glutamine isotopomers were generated from blood-borne (13) C-labeled glucose and lactate which were formed due to [1,2-(13) C[acetate metabolism of peripheral tissues. [4,5-(13) C] and [3,4,5-(13) C]glutamate and glutamine isotopomers were produced from [1,2-(13) C]acetyl-CoA that was derived from direct oxidation of [1,2-(13) C] acetate in the tumor. Major portion of C4 (13) C fractional enrichment of glutamate (93.3 ± 0.02%) and glutamine (90.9 ± 0.03%) were derived from [1,2-(13) C]acetate-derived acetyl-CoA.

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